This document summarizes the structure and role of the androgen receptor (AR) in prostate cancer. It discusses how AR is a ligand-dependent transcription factor that controls gene expression upon binding of ligands like dihydrotestosterone and testosterone. It has three domains - NTD, DBD and LBD. AR regulates genes involved in prostate cancer like the ETS family of transcription factors. Approximately 50% of prostate cancers upregulate ETS genes to promote cell proliferation. Antiandrogens used to treat prostate cancer work by competing with AR for binding sites to block the effects of dihydrotestosterone. The AR remains an important factor in prostate cancer progression and more research is focused on its mechanisms of action for developing improved treatments.

1. ANDROGEN RECEPTOR (AR):
Structure & Role In Prostate Cancer
DHARMENDRA MAURYA
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2. INTRODUCTION
 The androgen receptor (AR) belong to the steroid hormone group of
nuclear receptors with the estrogen receptor (ER), glucocorticoid
receptor (GR), mineralocorticoid receptor (MR) and progesterone
receptor (PR).
 The AR is a ligand-dependent transcription factor that controls the
expression of specific genes.
 The binding of the AR to its native ligands 5α-dihydrotestosterone
(DHT) and testosterone initiates male sexual development and
differentiation.
5α-reductase
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3.  Male sexual differentiation fails to occur in the absence of
androgens or without a functioning AR.
 A complete loss of AR function in males results in complete
androgen insensitivity syndrome.
www.voer.edu.vn
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4. ANDROGEN RECEPTOR (AR)
>located on long arm of X- chromosome
>110 kDa molecular wt. and 919 amino acid
long
NTD
(N-terminal domain)
DBD
(DNA binding
domain)
LBD
(C-terminal ligand
binding domain)
3 Domanis
>Highly Variable
>Poly-CAG & poly-GGC
>Highly conserve
>promote enhancer
region of AR regulating
gene
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5. Androgen Receptor (AR): Structure & Activity
Tan et. al : Acta Pharmacologica Sinica, 2015
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Tan et. al : Acta Pharmacologica Sinica, 2015

7. AR and Prostate Cancer
 E-twenty-six (ETS) family of transcription factor
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AR Regulated Promoter
region of target gene
(TMPRSS2)
Coding region of ETS Family
Approximately 50% of prostrate cancer
Upregulate the cell-cycle proliferation

8. Antiandrogen
Steroidal Non- steroidal
 Limited clinical application due
to many side effects.
 Lack androgenic properties.
 So, suitable for the treatment of
prostrate cancer.
Compete with AR for AR binding site.
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9. Conclusion
 the most commonly diagnosed cancer among American
men and the second leading cause of cancer deaths.
 On the basis of the AR and its mechanism to action on
targeting cells it regulated at several places such as
blocking of DHT synthesis.
 On the basis of androgen structure and function we can use
for the formation of several antiandrogen drugs in the
treatment of prostate cancer.
 The AR is still the “master regulator” of prostate cancer.
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10. Reference
 1. MH Eileen Tan et al.,Androgen receptor: structure, role in
prostate cancer and drug discovery,Acta Pharmacologica
Sinica (2015) 36: 3–23
 2. Davies P, Watt K, Kelly SM, Clark C, Price NC, McEwan IJ.
Consequences of poly-glutamine repeat length for the
conformation and folding of the androgen receptor amino-
terminal domain. J Mol Endocrinol 2008; 41: 301–14.
 3. Werner R, Holterhus PM, Binder G, Schwarz HP, Morlot M,
Struve D, et al. The A645D mutation in the hinge region of the
human androgen receptor (AR) gene modulates AR activity,
depending on the context of the polymorphic glutamine and
glycine repeats. J Clin Endocrinol Metab 2006; 91: 3515–20.
 4. Wang Q, Carroll JS, Brown M. Spatial and temporal
recruitment of androgen receptor and its coactivators involves
chromosomal looping and polymerase tracking. Mol Cell 2005;
19: 631–42.
 5. Haelens A, Tanner T, Denayer S, Callewaert L, Claessens F.
The hinge region regulates DNA binding,
nucleartranslocation,and transactivation of the androgen
receptor. Cancer Res 2007; 67: 4514–23.
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